Insulin

Insulin is a vital hormone in the regulation of the body’s metabolism. The hormone is produced by the beta cells of the pancreas. The hormone synthesis is in its pre-active form, known as preproinsulin, a single polypeptide hormone. The main function of the insulin hormone is to regulate the amount of glucose that enters the cells for respiration. It regulates the amount of glucose in the bloodstream, commonly known as blood sugar. When blood sugar is elevated, cells in the liver, muscle, and fat cells are activated by insulin to convert the excess glucose into glycogen, thereby reducing blood sugar levels. The cells store glycogen when energy requirements are high and are broken down into glucose by the glucagon hormone.

Insulin Imbalance

Low insulin levels in the body are associated with the pancreas’ beta cells’ inability to produce the hormone. The destruction of the beta cells of islets in the liver is the primary cause of the low insulin levels in the blood. Also, autoimmune destruction of islets caused by the presence of antibodies to insulin, tyrosine phosphate, beta-islet cells, and glutamic acid decarboxylase affects the balance of the hormone in the body. The autoimmune destruction has been linked to the inherent genes in a given population. It means specific genes are responsible for Human Lymphocyte Antigens (HLAs), resulting in diabetes type I. Thus, the destruction of the beta-cells of the liver is the primary cause that subjects the pancreas to the inability to synthesize the hormone responsible for blood sugar level regulation.

Some viruses destroy the cells resulting in a lack of insulin in the body. The major viruses include mumps virus and Coxsackie virus B1 and B4. Failure of insulin binding to the insulin receptor site, which has two glycoprotein subunits, results in a lack of reduced glucose permeability in the cells. Also, the defects of insulin receptors at the site significantly impact the functionality of insulin.

The low levels of insulin in the body increase the concentration of glucose. It results in diabetes mellitus type I and II depending on the cause. Destruction of beta-cells by viruses and autoimmune conditions cause type I diabetes, while insulin receptor defects at the site are associated with type II diabetes. Low insulin in the blood or malfunctioning insulin results in a condition known as hyperglycaemia. It is characterized by high sugar values of more than 200 mg/dL (11.1mmol/L) as opposed to the normal values of a healthy person, which are less than140 mg/dL (7.8mmol/L).

Effects of Insulin Imbalance

• Retinopathy is common among people living with hormone imbalance. It happens due to the proliferation of the blood vessels in the lens. The condition causes blurred vision, which is referred to as cataracts. When the condition remains unmanaged, it results in total blindness due to the formation of an opaque area in the eye lens.
• Excessive thirst and peeing among individuals with uncontrolled glucose levels are common. The blood’s osmotic pressure increases with high glucose levels due to the insulin imbalance. A lot of water is retained in the blood, which increases the kidney’s function to excrete excess glucose, making an individual feel thirsty and experience frequent urination.
• The individuals feel fatigued and more often associated with weight loss. Glucose is not readily available for respiration in the cells to yield energy important for metabolic activities. As such, individuals tend to feel tired due to a lack of energy and weight loss, an indication of malnutrition of the cells. Cell deprivation of insulin affects the conversion of excess glucose for storage in the fat, liver, and muscle cells resulting in weight loss. There are no energy reserves of glucose in the form of glycogen in individuals with low insulin levels or low insulin functionality.
• There is a tingling effect on the hands and feet. It is caused by neuropathy due to axonal degeneration of motor and sensory nerve demyelination as the conduction velocities are decreased. Other symptoms arise from neuropathy, including cardiac failure, excess sweating at night, and impotence in men.

Menopause and HRT

(i)

In the mid-40s, 95 % of women start experiencing oestrogen decline due to reduced ovary activities. By 50 years, 98 % of women will have experienced menopause due to a decline in oestrogen levels. The ovaries release fewer Luteinizing hormones (LH) and Follicle Stimulating Hormones (FSH), making it hard to regulate oestrogen production. Reducing oestrogen hormone levels to values less than 30 picograms per millilitre marks the beginning of the first stage of menopause, known as perimenopause. In over 90% of women, the period occurs between 3-5 years before menopause, the second stage, during the menopause stage, which takes place on average in women, aged 51 and 52 who miss their menstruation for 12 straight months. The oestrogen levels can drop to 0 picograms per millilitre in 99.9% of women due to a lack of ovulation. Besides, the third stage, post menopause, has oestrogen suppressed completely as it changes from estradiol to estrone.

(ii)

Oestrogen, known as estradiol, is synthesized from cholesterol in a series of reactions and intermediates. As women approach menopause, the activities of the estradiol pathway are decreased drastically in 98% of women by the formation of estrone which increases the amount of LDL cholesterol circulating in the blood from between 60%-70% to values above 90%. On the other hand, the amount of HDL cholesterol circulating in the body decreased from around 20%-33% to values less than 8%. The high level of LDL cholesterol builds up in the walls of blood vessels. The build-up, commonly referred to as plaque, reduces the diameter of the blood vessels, increasing blood pressure and bringing about cardiovascular diseases such as stroke and heart disease in 2 out of 10 women worldwide.

Oestrogen is important in enhancing bone maturation through epiphyseal growth plates. Reducing oestrogen levels in the body increases bone porosity and reduces bone mass in 80% of women over 50 years. Low oestrogen levels during menopause result in bone resorption due to the effect on osteoclast formation in 1 out of 10 women above 70 years. The bones gradually break down and release their minerals, subjecting the individuals to microstructures and loss of bone structure. Further, menopause is characterized by mood changes, sleeping problems, and weight gain. Some individuals might experience vaginal dryness, chills, and night sweats.

(iii)

Hormone Replacement Therapy (HRT) is a medical practice used by over 70% of women aged 50 years and above across developed countries to introduce artificial oestrogen in the body. HRT involving oestrogen can be targeted to correct the menopause symptoms for the affected women. Between 2009 and 2019, oestrogen was delivered to  8 out of 10 women across Europe aged 50 years and above in the form of a skin patch, pill or ring systematically for absorption in the body. The introduction of systemic oestrogen helps to reduce bone resorption as normal osteoclast formation is attained.

(iv)

Oestrogen HRT has many benefits for women who start experiencing menopause symptoms. The systemic delivery of the hormone helps to reduce night sweats, vaginal dryness, and hot flashes when applied in the form of the cream to up to 98% of female patients aged 50 years and above. Further, it helps to make sex a less painful experience and helps individuals have a better sleep. Other benefits include the reduction of bone fractures due to preventing osteoporosis.

HRT has been found to cause multiple risks, such as breast, ovarian, uterus, and colon cancer, in 10% of the population. When oestrogen is administered, progesterone monitoring is important to reduce these risks. The physicians recommend the administration of progesterone for women with an intact uterus. Oestrogen, when not in good check with the progesterone, increases the uterine wall’s thickening, which increases the risk of an individual developing endometrial cancer. Between 1999 and 2009, in 90% of women that used the oestrogen HRT, 10%  were subjected to chemotherapy to treat underlying cancer.

Breast, colon, and ovarian cancer are likely due to long exposure to oestrogen in 1 out of 10 women of an average age of 65 years. The hormone must be kept in check by progesterone, which regulates the cell proliferation initiated by the oestrogen. Long exposure to the hormone of up to 10 years subjects the ovaries and breasts to uncontrolled proliferation of the cells, which can mark the beginning of cancer when progesterone is not in check. The HRT of oestrogen increases the risk of heart disease due to increased LDL levels. Other risks include stroke and blood clots.